Functions of the stress-signaling kinase SEK1 in mouse immune System and development
应激信号激酶SEK1在小鼠免疫系统和发育中的功能
基本信息
- 批准号:10680599
- 负责人:
- 金额:$ 1.98万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The stress signal kinase SEK1/MKK4 is a direct activator of stress-activated protein kinase (SAPKs ; also called c-Jun-N- terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damages, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1ィイD1-/-ィエD1 embryos displayed severe anemia and died between embryonic day 10.5(E10.5) and E12.5. In the present study, we investigated the functions and properties of SEK1 and its related kinase, SEK2/MKK7. 1. Hematopoiesis and vasculogenesis are normal in sek1ィイD1-/-ィエD1 embryos. However, hepatogenesis and liver formation were severely impaired in the mutant embryos and E11.5 and E12.5 sek1ィイD1-/-ィエD1 embryos had greatly reduced numbers of parenchymal hepatocytes. Sek1ィイD1-/-ィエD1 liver cells underwent massive apoptosis. These results provide the first genetic link between SEK1 and organogenesis in mammals and indicate that SEKI provides a crucial and specific survival signal for hepatocytes. 2. We disrupted the sek2 gene in mouse embryonic stem (ES) cells using the Cre-10xP system. Sek2ィイD1-/-ィエD1 ES cells did not grow and died, Thus. SEK2 is a crucial survial molecule for ES cells. 3. We prepared monoclonal antibodies to mouse fetal liver. One of them, anti-Liv1 specifically recognized hepatocytes in wild-type embryos, but not in sek1ィイD1-/-ィエD1 embryos. These results indicate that SEK1 regulates Liv1 expression and fetal liver development.
应激信号激酶SEK 1/MKK 4是应激活化蛋白激酶(SAPKs ;也称为c-Jun-N-末端激酶,JNK)的直接激活剂,其响应于多种细胞应激,例如渗透压的变化、代谢毒物、DNA损伤、热休克或炎性细胞因子。我们已经破坏了sek 1基因在小鼠中使用同源重组。Sek 1胚胎D1-/-Ek 1胚胎D1表现出严重的贫血,并在胚胎第10.5天(E10.5)和E12.5之间死亡。在本研究中,我们研究了SEK 1及其相关激酶SEK 2/MKK 7的功能和性质。1. sek 1胚胎D1-/-胚胎D1的造血和血管发生是正常的。然而,在突变胚胎中肝发生和肝脏形成严重受损,E11.5和E12.5 sek 1 Ek 1 D1-/-Ek 1 D1胚胎的实质肝细胞数量大大减少。Sek 1 β D1-/-β D1肝细胞发生大量凋亡。这些结果提供了SEK 1与哺乳动物器官发生之间的第一个遗传联系,并表明SEKI为肝细胞提供了关键和特异性的存活信号。2.我们使用Cre-10 xP系统在小鼠胚胎干(ES)细胞中破坏sek 2基因。Sek 2 ES细胞不生长,死亡。SEK 2是ES细胞的重要存活分子。3.制备了鼠胎肝单克隆抗体。其中之一,抗Liv 1特异性地识别野生型胚胎中的肝细胞,但不识别sek 1胚胎D1-/-胚胎D1中的肝细胞。这些结果表明,SEK 1调节Liv 1表达和胎肝发育。
项目成果
期刊论文数量(23)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
H. Nishina, et al.: "Impact TCR-mediated apoptosis and Bcl-XL expression in T cells lacking the stress kinase activator SEK1/MKK4"J. Immunol.. 161. 3416-3420 (1998)
H. Nishina 等人:“在缺乏应激激酶激活剂 SEK1/MKK4 的 T 细胞中影响 TCR 介导的细胞凋亡和 Bcl-XL 表达”J。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
K. Bachmaier, C. Krawczyk, I. Kozieradzki, Y. Y. Kong, T. Sasaki, A. Oliveira-dos-Santos, S. Mariathasan, D. Bouchard, A. Wakeham, A. Itie, J. Le, P. Ohashi, I. Sarosi, I., H. Nishina, S. Lipkowitz, and J. M. Penninger: "Negative regulation of lymphocyte
K. Bachmaier、C. Krawczyk、I. Kozieradzki、Y. Y. Kong、T. Sasaki、A. Oliveira-dos-Santos、S. Mariathasan、D. Bouchard、A. Wakeham、A. Itie、J. Le、P. Ohashi
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
K. D. Fischer, Y. Y. Kong, H. Nishina, K. Tedford, L. Marengere, I. Kozieradzki, T. Sasaki, M. Starr. G. Chan, S. Gardener, M. P. Nghiem, D. Bouchard, M. Barbacid, A. Bernstein, and J. M. Penninger: "Vav is a regulator of cytoskeletal reorganization media
K. D. Fischer、Y. Y. Kong、H. Nishina、K. Tedford、L. Marengere、I. Kozieradzki、T. Sasaki、M. Starr。
- DOI:
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- 影响因子:0
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- 通讯作者:
K.Bachmaier, et al.: "Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b."Nature. 403. 211-216 (2000)
K.Bachmaier 等人:“分子接头 Cbl-b 对淋巴细胞活化和自身免疫的负调节。”《自然》。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
H. Nishina, L. Radvanyl, K. Raju, T. Sasaki, I. Kozieradzki, and J. M. Penninger: "Impaired TCR-mediated apoptosis and Bcl-XL expression in T cells lacking the stress kinase activator SEK1/MKK4."J. Immunol.. 161. 3416-3420 (1998)
H. Nishina、L. Radvanyl、K. Raju、T. Sasaki、I. Kozieradzki 和 J. M. Penninger:“缺乏应激激酶激活剂 SEK1/MKK4 的 T 细胞中 TCR 介导的细胞凋亡和 Bcl-XL 表达受损。”
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NISHINA Hiroshi其他文献
NISHINA Hiroshi的其他文献
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{{ truncateString('NISHINA Hiroshi', 18)}}的其他基金
Analysis of cellular quality control in liver tissue formation
肝组织形成中的细胞质量控制分析
- 批准号:
26293012 - 财政年份:2014
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of YAP-dependent gene expression that regulates organ size.
分析调节器官大小的 YAP 依赖性基因表达。
- 批准号:
25670021 - 财政年份:2013
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of YAP-dependent hepatic tumor formation and analysis of global expression of related microRNAs
YAP依赖性肝肿瘤形成的进展及相关microRNA的整体表达分析
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24659030 - 财政年份:2012
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$ 1.98万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Analysis of signaling pathways involved in liver development, regeneration and disease using mice and medaka
使用小鼠和青鳉分析涉及肝脏发育、再生和疾病的信号通路
- 批准号:
23390018 - 财政年份:2011
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Establishment of YAP-dependent hepatic tumor formation and global expression analysis of related microRNAs
YAP依赖性肝肿瘤形成的建立及相关microRNA的整体表达分析
- 批准号:
23659034 - 财政年份:2010
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Construction and analysis of model organisms for human liver diseases
人类肝脏疾病模型生物的构建与分析
- 批准号:
20390022 - 财政年份:2008
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of Mutation Affecting Liver Function and Regeneration in Model Organisms
影响模式生物肝功能和再生的突变分析
- 批准号:
18390021 - 财政年份:2006
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$ 1.98万 - 项目类别:
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Regulation of cellular localization and activation of the transpotsome by G proteins and MAP kinases
G 蛋白和 MAP 激酶对细胞定位和转座体激活的调节
- 批准号:
17081005 - 财政年份:2005
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$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Identification of hepatic stem cells and development of its separation methods : Analysis of the self-replication and survival of the cells
肝干细胞的鉴定及其分离方法的开发:分析细胞的自我复制和存活
- 批准号:
13558083 - 财政年份:2001
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$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Signal transduction mechanisms involved in mouse embryonic liver formation
小鼠胚胎肝脏形成中涉及的信号转导机制
- 批准号:
12470493 - 财政年份:2000
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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